Interleukin-1β overproduction is a common cause for neuropathic pain, memory deficit, and depression following peripheral nerve injury in rodents

Wen Shan Gui, Xiao Wei, Chun Lin Mai, Madhuvika Murugan, LongJun Wu, Wen Jun Xin, Li Jun Zhou, Xian Guo Liu

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Background: Chronic pain is often accompanied by short-term memory deficit and depression. Currently, it is believed that short-term memory deficit and depression are consequences of chronic pain. Here, we test the hypothesis that the symptoms might be caused by overproduction of interleukin-1beta (IL-1β) in the injured nerve independent of neuropathic pain following spared nerve injury in rats and mice. Results: Mechanical allodynia, a behavioral sign of neuropathic pain, was not correlated with short-term memory deficit and depressive behavior in spared nerve injury rats. Spared nerve injury upregulated IL-1β in the injured sciatic nerve, plasma, and the regions in central nervous system closely associated with pain, memory and emotion, including spinal dorsal horn, hippocampus, prefrontal cortex, nucleus accumbens, and amygdala. Importantly, the spared nerve injury-induced memory deficits, depressive, and pain behaviors were substantially prevented by peri-sciatic administration of IL-1β neutralizing antibody in rats or deletion of IL-1 receptor type 1 in mice. Furthermore, the behavioral abnormalities induced by spared nerve injury were mimicked in naïve rats by repetitive intravenous injection of re combinant rat IL-1β (rrIL-1β) at a pathological concentration as determined from spared nerve injury rats. In addition, microglia were activated by both spared nerve injury and intravenous injection of rrIL-1β and the effect of spared nerve injury was substantially reversed by peri-sciatic administration of anti-IL-1β. Conclusions: Neuropathic pain was not necessary for the development of cognitive and emotional disorders, while the overproduction of IL-1β in the injured sciatic nerve following peripheral nerve injury may be a common mechanism underlying the generation of neuropathic pain, memory deficit, and depression.

Original languageEnglish (US)
JournalMolecular Pain
Volume12
DOIs
StatePublished - May 3 2016
Externally publishedYes

Fingerprint

Peripheral Nerve Injuries
Memory Disorders
Neuralgia
Interleukin-1
Interleukin-1beta
Rodentia
Depression
Wounds and Injuries
Short-Term Memory
Sciatic Nerve
Intravenous Injections
Chronic Pain
Interleukin Receptors
Pain
Hyperalgesia
Nucleus Accumbens
Microglia
Neutralizing Antibodies
Amygdala
Prefrontal Cortex

Keywords

  • depression
  • interleukin-1β
  • microglia
  • Neuropathic pain
  • peripheral nerve injury
  • short-term memory deficit

ASJC Scopus subject areas

  • Molecular Medicine
  • Cellular and Molecular Neuroscience
  • Anesthesiology and Pain Medicine

Cite this

Interleukin-1β overproduction is a common cause for neuropathic pain, memory deficit, and depression following peripheral nerve injury in rodents. / Gui, Wen Shan; Wei, Xiao; Mai, Chun Lin; Murugan, Madhuvika; Wu, LongJun; Xin, Wen Jun; Zhou, Li Jun; Liu, Xian Guo.

In: Molecular Pain, Vol. 12, 03.05.2016.

Research output: Contribution to journalArticle

Gui, Wen Shan ; Wei, Xiao ; Mai, Chun Lin ; Murugan, Madhuvika ; Wu, LongJun ; Xin, Wen Jun ; Zhou, Li Jun ; Liu, Xian Guo. / Interleukin-1β overproduction is a common cause for neuropathic pain, memory deficit, and depression following peripheral nerve injury in rodents. In: Molecular Pain. 2016 ; Vol. 12.
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AU - Gui, Wen Shan

AU - Wei, Xiao

AU - Mai, Chun Lin

AU - Murugan, Madhuvika

AU - Wu, LongJun

AU - Xin, Wen Jun

AU - Zhou, Li Jun

AU - Liu, Xian Guo

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N2 - Background: Chronic pain is often accompanied by short-term memory deficit and depression. Currently, it is believed that short-term memory deficit and depression are consequences of chronic pain. Here, we test the hypothesis that the symptoms might be caused by overproduction of interleukin-1beta (IL-1β) in the injured nerve independent of neuropathic pain following spared nerve injury in rats and mice. Results: Mechanical allodynia, a behavioral sign of neuropathic pain, was not correlated with short-term memory deficit and depressive behavior in spared nerve injury rats. Spared nerve injury upregulated IL-1β in the injured sciatic nerve, plasma, and the regions in central nervous system closely associated with pain, memory and emotion, including spinal dorsal horn, hippocampus, prefrontal cortex, nucleus accumbens, and amygdala. Importantly, the spared nerve injury-induced memory deficits, depressive, and pain behaviors were substantially prevented by peri-sciatic administration of IL-1β neutralizing antibody in rats or deletion of IL-1 receptor type 1 in mice. Furthermore, the behavioral abnormalities induced by spared nerve injury were mimicked in naïve rats by repetitive intravenous injection of re combinant rat IL-1β (rrIL-1β) at a pathological concentration as determined from spared nerve injury rats. In addition, microglia were activated by both spared nerve injury and intravenous injection of rrIL-1β and the effect of spared nerve injury was substantially reversed by peri-sciatic administration of anti-IL-1β. Conclusions: Neuropathic pain was not necessary for the development of cognitive and emotional disorders, while the overproduction of IL-1β in the injured sciatic nerve following peripheral nerve injury may be a common mechanism underlying the generation of neuropathic pain, memory deficit, and depression.

AB - Background: Chronic pain is often accompanied by short-term memory deficit and depression. Currently, it is believed that short-term memory deficit and depression are consequences of chronic pain. Here, we test the hypothesis that the symptoms might be caused by overproduction of interleukin-1beta (IL-1β) in the injured nerve independent of neuropathic pain following spared nerve injury in rats and mice. Results: Mechanical allodynia, a behavioral sign of neuropathic pain, was not correlated with short-term memory deficit and depressive behavior in spared nerve injury rats. Spared nerve injury upregulated IL-1β in the injured sciatic nerve, plasma, and the regions in central nervous system closely associated with pain, memory and emotion, including spinal dorsal horn, hippocampus, prefrontal cortex, nucleus accumbens, and amygdala. Importantly, the spared nerve injury-induced memory deficits, depressive, and pain behaviors were substantially prevented by peri-sciatic administration of IL-1β neutralizing antibody in rats or deletion of IL-1 receptor type 1 in mice. Furthermore, the behavioral abnormalities induced by spared nerve injury were mimicked in naïve rats by repetitive intravenous injection of re combinant rat IL-1β (rrIL-1β) at a pathological concentration as determined from spared nerve injury rats. In addition, microglia were activated by both spared nerve injury and intravenous injection of rrIL-1β and the effect of spared nerve injury was substantially reversed by peri-sciatic administration of anti-IL-1β. Conclusions: Neuropathic pain was not necessary for the development of cognitive and emotional disorders, while the overproduction of IL-1β in the injured sciatic nerve following peripheral nerve injury may be a common mechanism underlying the generation of neuropathic pain, memory deficit, and depression.

KW - depression

KW - interleukin-1β

KW - microglia

KW - Neuropathic pain

KW - peripheral nerve injury

KW - short-term memory deficit

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